Casein kinase Iε in the Wnt pathway:: Regulation of β-catenin function

Wnt and its intracellular effector beta-catenin regulate developmental and oncogenic processes. Using expression cloning to identify novel components of the Wnt pathway, we isolated casein kinase I epsilon (CKI epsilon). CKI epsilon mimicked Wnt in inducing a secondary axis in Xenopus, stabilizing beta-catenin, and stimulating gene transcription in cells, Inhibition of endogenous CKI epsilon by kinase-defective CKI epsilon or CKI epsilon antisense-oligonucleotides attenuated Wnt signaling. CKI epsilon was in a complex with axin and other downstream components of the Wnt pathway, including Dishevelled, CKI epsilon appears to he a positive regulator of the pathway and a link between upstream signals and the complexes that regulate beta-catenin.